Human plasma low density lipoproteins (LDL) represent the major carrier of cholesterol in the circulation. LDL consist of approximately 75% lipid and 25% protein. The major lipids are cholesteryl esters, unesterified cholesterol and phospholipid; phosphatidylcholine accounts for 75% of the total phospholipid, with sphingomyelin accounting for the remainder. The major protein constituent of human plasma LDL is apolipoprotein B (apoB). The apparent molecular weight of apoB by polyacrylamide gel electrophoresis in sodium dodecyl sulfate is 550,000. By analytical ultracentrifugation in 6 M guanidine, apoB has a molecular weight of 225,000. The amino acid sequence of apoB is not known. In addition to binding and transporting lipids, apoB plays an important role in lipoprotein metabolism by its interaction with specific cell surface receptors. The long-range objectives of this research are to elucidate the structure of apoB and, in particular, to define the amino acid sequence domains of apoB which interact with lipid, cell surface receptors, and heparin. The methods include techniques of protein chemistry, amino acid sequencing, physical chemistry, cell biology and immunochemistry. In addition to defining the lipid-binding, heparin-binding, and cell receptor-binding domains of apoB, the relationship of these domains to antigenic determinants will also be determined using monoclonal antibodies. It is anticipated that detailed knowledge of the structure of apoB and the relationship of structure to function will contribute to our overall understanding of the factors which regulate the metabolism of human plasma LDL. Since LDL lipids are the major contributor to atherosclerotic lesion, it will then be possible to understand the basic processes of atherosclerosis.